Sumoylation at the Host-Pathogen Interface

Wilson, Van G.

A large number of pathogen proteins have been shown to target the sumoylation system in order to modulate overall sumoylation levels in the host cell. Many pathogen express proteins that target Ubc9, the SUMO conjugation enzyme, but in some cases other sumoylation enzymes are also targeted. The one known example of a pathogen protein that targets the SUMO activating enzyme (SAE) is the Chicken Embryo Lethal Orphan (CELO) adenovirus GAM1 protein [80] . GAM1 is critical for CELO replication [81] , and it was quickly shown that GAM1 expression decreased sumoylation of the HDAC1 histone deacetylase [82] . A subsequent study revealed that GAM1 expression leads to a dramatic decrease in total SUMO conjugated products in the cell, that GAM1 binds the SAE1/2 SUMO activation enzyme and inhibits its activity in vitro, and also strongly reduced intracellular levels of SAE1, SAE2, and Ubc9 [80] . Boggio et al. further demonstrated that GAM1 binds the cullin proteins, Cul2 and Cul5, and recruits the Cul2/5-EloB/C-Roc1 ubiquitin ligase complexes to SAE1/2 [83] .